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Vaccine
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ICO Monograph Series on HPV and Cervical Cancer: Latin America and the Caribbean Regional Report
a r t i c l e
Keywords:
HPV
HPV testing
Latin America
Caribbean
Cervical cancer
Screening
Cytology
i n f o
a b s t r a c t
Cervical cancer remains an important public health problem in the Latin America and Caribbean region
(LAC), with an expected signicant increase in disease burden in the next decades as a result of population
ageing. Prophylactic human papillomavirus (HPV) vaccine is currently unaffordable in LAC countries.
However, even if vaccination was implemented, an additional two decades will be required to observe
its impact on HPV related disease and cancer. With some exceptions, cytology-based screening programs
have been largely ineffective to control the problem in the region, and there is a need for new approaches
to the organization of screening and for use of newly developed techniques. Several research groups in
LAC have conducted research on new screening methods, some of which are summarized in this paper.
A recommendation to reorganize screening programs is presented considering visual inspection for very
low resource areas, improvement of cytology where it is operating successfully and HPV DNA testing
followed by visual inspection with acetic acid (VIA) or cytology as soon as this method becomes technically
and economically sustainable. This could be facilitated by the incorporation of new, low-cost HPV DNA
testing methods and the use of self-collected vaginal specimens for selected groups of the population. An
important requisite for screening based on HPV testing will be the quality assurance of the laboratory and
the technique by validation and certication measures.
2008 Elsevier Ltd. All rights reserved.
1. Introduction
Efforts to control cervical cancer in the Latin America and
Caribbean region (LAC) have been largely unsuccessful. Recent estimates predict that if current incidence rates remained unchanged,
by 2025, countries in LAC would face an increase of nearly 75% in
the number of cases solely as a consequence of population ageing.
This could represent more than 50,000 additional cases per year,
raising the total to more than 126,000 with about 60,000 deaths
per year [1].
Prophylactic human papillomavirus (HPV) vaccines will take
years to become affordable as public health interventions in LAC,
and even more time to affect cervical cancer rates [2,3]. Therefore,
Corresponding author. Tel.: +506 2220 3039; fax: +506 2291 0832.
E-mail address: rherrero@amnet.co.cr (R. Herrero).
0264-410X/$ see front matter 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.vaccine.2008.05.025
it is imperative for governments to establish cervical cancer screening and treatment programs aimed at preventing the hundreds of
thousands of deaths that will occur in LAC before the vaccine starts
having an impact on the disease.
The basis of programs that have reduced cervical cancer in
developed countries is mass screening with cytology, followed
by colposcopy, biopsy and treatment as needed. Each of these
procedures has important technical limitations, and successful secondary prevention of cervical cancer requires repeated testing
every one to three years and intensive workup procedures, making the multi-visit process very complex and expensive. Although
the elements of successful programs have been known for many
decades, the resources or the political will to make the necessary
investments have been lacking in most developing countries. In
addition, womens health priorities linked to their education and
competing needs have hampered these efforts in low-resource settings.
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Table 1
Performance of single and selecteda two test strategies for detection of cervical intraepithelial neoplasia grade 3 or worse (CIN3+). Guanacaste, Costa Rica
Estrategyb
Sensitivityc
Specicityd
Youdens Indexe
HPV (+)
Liquid-based Cytology ( ASC-US)
Pap Smear ( ASC-US)
Cervigram ( A)
Pap Smear ( HSIL) or HPV (+)
Liquid-based Cytology ( HSIL) or HPV (+)
Cervigram ( P2) or HPV (+)
Liquid-based Cytology ( ASC-US) or Cervigram ( P0)
Pap Smear ( HSIL) or liquid-based cytology ( ASC-US)
Pap Smear ( LSIL) or Cervigram ( P0)
85.3
87.5
63.0
61.7
90.7
90.5
89.7
93.2
86.5
74.5
88.2
87.8
93.7
84.8
87.8
88.0
88.1
83.9
87.6
90.9
0.74
0.74
0.57
0.46
0.79
0.78
0.78
0.77
0.74
0.65
0.670.80
0.670.80
0.480.66
0.370.56
0.730.84
0.730.84
0.720.84
0.720.82
0.680.81
0.570.74
ASC-US: Atypical squamous cells of undetermined signicance; HSIL: High-grade squamous intraepithelial lesions; LSIL: Low-grade squamous intraepithelial lesions. A:
Atypical.
Reproduced from Ferreccio C et al. 2003 [7].
a
For each of the six possible two-technique combinations, the table shows the performance for the cut-points with the highest accuracy as measured by Youdens index.
b
There were three possible thresholds for conventional and liquid-based cytology (ASC-US, LSIL, HSIL), ve possible thresholds for Cervigram [Atypical (A), Positive 0 (P0),
Positive 1 (P1), Positive 2 (P2), Positive 3 (P3)], and a single threshold for HPV DNA testing (positive versus negative). Techniques were considered singly and in pairs at all
thresholds. Two kinds of combinations were evaluated, either requiring both techniques to be positive or at least one. Overall, there were 112 strategies considered, which
were ranked in order of decreasing Youdens index.
c
Sensitivity calculated as the percentage of cases of >=CIN3 detected by the screening strategy.
d
Specicity calculated as the percentage of women without CIN3 or cancer who tested negative by the screening strategy.
e
Youdens index calculated as sensitivity plus specicity (expressed as proportions) minus 1.00, with 95% condence interval. The values range theoretically from 1.0
(perfect) to 0.0 (randomly useless) to 1.0 (always wrong).
New approaches to cervical cancer screening are needed to overcome the technical limitations, simplify the process and render it
more feasible and acceptable to women in limited resource areas.
Several of these approaches take advantage of the current understanding of the natural history of the disease and new technological
developments (e.g., HPV DNA testing) are being evaluated in trials
and demonstration projects. These approaches need to be already
under active discussion among public health decision makers and
womens organizations for timely implementation.
Several institutions in LAC are conducting research to evaluate
some of these new methods. Although in the Caribbean region there
are limited data on screening, the burden of disease is similar to
Latin American nations and cervical cancer screening programs for
secondary prevention are also necessary. In this article, we summarize the most salient research efforts and discuss some potential
new approaches to cervical cancer control in different settings of
LAC according to their level of development and infrastructure.
2. Research activities on screening methods in Latin
America
2.1. Evaluation of screening techniques in Costa Rica: the
Guanacaste Project
In the population-based cohort study conducted in Guanacaste
in 199394 [4], the performance of conventional cytology, liquidbased cytology (LBC) [5], HPV testing for 13 carcinogenic types
with MY09-11 polymerase chain reaction (PCR), Hybrid Capture
2 (HC2), Qiagen Gaithersburg, Inc., MD, USA (previously Digene
Corp.) and CervigramTM , National Testing Laboratories, Fenton, MO
[6] were evaluated. The tests were applied concurrently to more
than 8,500 women [7]. The nal reference diagnosis for study
endpoint was histologically-conrmed cervical intraepithelial neoplasia grade 3 or worse (CIN3+) at enrollment or during follow-up.
Conventional cytology was interpreted in Costa Rica, the other
techniques in the United States of America (USA). Sensitivity and
specicity of each technique were analyzed individually and in
paired combinations, using Youdens index as a summary measure
of test accuracy (Table 1).
As single techniques, LBC or PCR HPV DNA testing were signicantly more accurate than cytology or Cervigram, particularly
among older women. Cervigram was the least accurate test of any.
Considering two tests in combination with either LBC or PCR HPV
testing, accuracy was not substantially increased in comparison to
either test alone. A possibly useful synergy was observed between
conventional cytology and Cervigram, suggesting that these techniques together, cytological and visual may provide an increased
benet.
The sensitivity of LBC was considerably higher than that of
conventional cytology, although the tests were not interpreted by
the same cytopathologists. On the other hand, HPV testing and
LBC had lower positive predictive values than conventional cytology (Table 2). Cytological techniques, highly observer-dependent,
performed better than usually reported, a poorer performance is
expected in real life than in this highly controlled research study.
The performance of HC2, the only Food and Drug Administration
(FDA)-approved HPV testing method, which detects the combined
presence of 13 cancer-associated HPV types (HPV-16, 18, 31, 33, 35,
39, 45, 51, 52, 56, 58, 59, and 68) was also evaluated. This methodology had a testing sensitivity of 88.4% and a specicity of 89.0% for
high-grade lesions and cancer (all cancer cases tested HPV positive
with HC2) [8].
The Guanacaste study demonstrated that HPV testing and possibly LBC are more sensitive than conventional cytology. In LAC,
many women will have few contacts with screening programs,
making a screening test of high sensitivity and negative predictive
value preferable. HPV tests and LBC accomplished that requirement in Guanacaste, but the former is easier to standardize and
is highly reproducible, possibly providing more consistent results
in different scenarios. Better sensitivity of HPV testing has been
demonstrated in multiple studies, but that of LBC remains controversial [9].
2.2. Evaluation of screening techniques in San Martn. Per: the
TATI Project
The TATI project (Spanish acronym for screening and immediate treatment) was conducted to investigate screening tests that
are potentially more appropriate in high incidence areas with limited resources [10]. More than 30,000 women aged 2549 years;
with an intact uterus and no past history of conization were
screened with visual inspection with acetic acid (VIA) and con-
Positive predictive
valuec
Liquid-based cytology
(ASC-US)
HPV (+)
Pap Smear (ASC-US)
Cervigram (A)
Pap Smear (HSIL) or HPV (+)
Liquid-based cytology (HSIL) or
HPV (+)
Cervigram (P2) or HPV (+)
Liquid-based cytology
(ASC-US) or Cervigram (P0)
8.5%
99.8%
8.6%
11.5%
4.9%
8.8%
9.0%
99.8%
99.5%
99.4%
99.9%
99.9%
8.8%
7.0%
99.9%
99.9%
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Table 3
Positivity rates of screening with different methods among 5,435 women aged 2549 years in the TATI project
Age
N total
25-29
30-34
35-39
40-44
45-49
All ages
1,480
1,463
1,223
769
500
5,435
VIA
366
376
311
166
98
1,317
24.7
25.7
25.4
21.6
19.6
24.2
16
25
22
21
13
97
1.1
1.7
1.8
2.7
2.6
1.8
227
231
228
134
99
919
15.3
15.8
18.6
17.4
19.8
16.9
229
182
145
88
43
687
15.5
12.4
11.9
11.4
8.6
12.6
VIA: Visual inspection with acetic acid; RLU: Relative light unit; ASC-US: Atypical squamous cells of undetermined signicance.
Adapted from Almonte M et al. 2007 [10].
a
Percentage including those with missing or inadequate test samples.
L52
Table 4
Sensitivity, specicity and positive predictive values of screening tests in 5,435 women, TATI Project
Sensitivity (95% Cl) forb
CIS+ (N = 85.5)
Moderate Dysplasia+
VIA
54.90
(47.062.7)
48.06
(38.757.3)
41.18
(30.552.0)
76.70
(75.577.8)
6.65
(5.38.0)
VIA + M
42.79
(34.750.9)
36.24
(27.245.6)
31.36
(21.341.6)
90.96
(90.291.7)
12.40
(9.615.2)
PAPa
26.21
(19.033.6)
33.61
(24.442.8)
42.54
(31.553.8)
98.68
(98.399.0)
37.93
(28.147.5)
69.66
(62.276.8)
76.57
(68.184.2)
80.28
(71.188.7)
83.71
(82.784.7)
11.69
(9.613.8)
64.70
(56.872.0)
73.36
(60.677.6)
77.32
(67.786.0)
86.69
(85.787.6)
13.07
(10.615.5)
89.42
(83.394.6)
95.78
(91.199.4)
89.32
(88.590.1)
17.95
(15.020.9)
LBC
ASCUS
LSIL
2RLU
72.77
(65.679.5)
84.96
(78.191.2)
89.85
(82.995.7)
90.45
(89.791.2)
18.73
(15.621.9)
4RLU
70.02
(62.776.9)
83.0
(75.889.5)
88.49
(81.494.7)
91.58
(90.892.3)
20.09
(16.723.5)
VIA or PAPa
66.76
(58.874.4)
64.51
(55.273.5)
62.36
(51.072.9)
76.34
(75.177.6)
7.99
(6.49.6)
CIS: Carcinoma in situ; PPV: Positive predictive value; VIA: Visual inspection with acetic acid; VIA + M: VIA aided by a magnication device after a VIA positive exam; RLU:
Relative light unit; ASC-US: Atypical squamous cells of undetermined signicance; LSIL: Low-grade squamous intraepithelial lesions; CI: Condence interval.
Reproduced from Almonte M et al. 2007 [10].
a
PAP = Conventional cytology ASC-US or worse.
b
Histology was carried out in a laboratory in Lima and was reported using a standard Peruvian classication (which includes moderate and severe dysplasia, carcinoma
in situ and cancer). Roughly speaking, severe dysplasia and carcinoma in situ should correspond to CIN3 and moderate dysplasia to CIN2.
cal cancers are found in women who have never been screened.
An alternative for women who reject the pelvic examination is
self-collected (SC) vaginal sampling obtained at home. In a nationwide study of Chilean women in 2003, there was high participation
(83.1%) by patients and health workers, providing samples adequate
for HPV testing. The most frequent high-risk HPV types detected
from vaginal samples were similar to those types identied in previous studies using cervical samples [15].
A follow-up study (20062009) of women from a prevalence
survey [16] used self-sampling at home and cytology at the clinic,
with participation rates of 91.4% and 70.7%, respectively. Preliminary results show a very high rate of -globin positivity (96.2%
and 97.5%, respectively) indicating that SC vaginal samples are of
very good quality, comparable with cervical samples. A higher rate
of HPV detection in the vaginal than in the cervical samples was
noted (23.2% and 14.7%, respectively). The impact of the increased
HPV detection on the sensitivity and specicity to detect cervical
cancer precursors needs to be investigated.
Both population-based studies demonstrated that self-sampling
can be easily incorporated in LAC as part of an HPV based screening program and it has the advantage of allowing better allocation
of human resources and increasing access to certain subgroups of
women who are isolated or reluctant to be examined. Its main
limitations are inherent to the current HPV testing itself: cost and
limited specicity.
2.4. HPV testing as primary screening at the Mexican Institute for
Social Security (IMSS), Morelos, Mexico
To evaluate whether HPV testing is more effective than cytology
[17], SC, HPV test clinician-collected (CC) HPV test and cytology
were compared. The HPV HC2 test was performed both on the SC
and CC samples. All women attending screening at 23 health units
were invited in 1999. Women with history of CIN2/3 or cancer, previous hysterectomy, or pregnant were excluded. A total of 7,868
women between the ages of 15 and 85 (median age = 41 years)
participated (response rate: >95%).
Detection rates of high-risk HPV types in the SC and CC specimens were 11.6% and 9.4%, respectively. The relative sensitivity of
cytology to detect CIN2/3 or cancer was lower (59.4%), as compared
to 71.3% (p = 0. 008) for SC, and 93.1% (p = 0.0001) for CC (Table 5).
The relative specicity was 98.6%, 90.4%, and 92.8% for cytology, SC and CC, respectively. Negative predictive values were 99.4%,
99.5% and 99.9%, and colposcopy referral was 2.8%, 11.0% and 6.7%.
HPV testing showed higher sensitivity than cytology and the
CC HPV test showed the highest sensitivity for detection of cer-
Table 5
Performance of the Pap smear, HPV self-collected (SC) and HPV clinician-collected (CC) testing strategies for cervical cancer screening in Mexico
Test
Pap smear
HPV-SC
HPV-CC
59.40 (49.1668.92)
98.59 (98.2998.84)
36.36 (29.1244.24)
99.44 (99.2499.59)
71.28 (61.2979.30)
90.37 (89.6891.03)
9.09 (7.2211.36)
99.57 (99.3799.70)
93.06 (85.7596.92)
92.82 (92.2193.39)
14.89 (12.2517.97)
99.89 (99.7899.95)
88.34 (80.0593.61)
89.11 (88.3889.90)
9.86 (8.0312.03)
99.82 (99.6899.90)
97.18 (91.1499.30)
91.52 (90.8692.13)
13.38 (11.0416.11)
99.95 (99.8699.98)
HPV-SC: Self-collected HPV HC2 test; HPV-CC: Clinician-collected HPV HC2 test; CI: Condence interval.
Reproduced from Salmeron J et al. 2003 [17].
L53
Table 6
Estimated detection rates of underlying high-grade squamous intraepithelial lesion (HSIL) or cervical cancer by a conventional cytology test and a self-collected (SC) HPV test
Estimated detection rate
Cervical cytology
Fig. 1. Screening and follow-up algorithms in the 50,000-women community trial among women from the Mexican Institute of Social Security (20052009).
Percentages and absolute numbers are the expected for each group and branch. Pap: Papanicolaou test; HPV: HPV DNA test; TX: treatment.
Source of data: Lazcano-Ponce E et al. submitted 2008.
L54
Table 7
Elements required for a successful screening program
Central coordination
Information system
Quality assurance of all aspects of the program
Uniformity of activities and operating procedures
Denition of target groups (avoidance of low risk groups, e.g. very young women)
Denition and adherence to screening intervals
High coverage of the population selected
Adequate follow up of abnormalities
Assurance of timely treatment of lesions detected
Consideration of other womens health needs in the area
Communication and educational strategies
Evaluation
Adoption of a clinically validated screening test
Adoption of a clinically validated triage and diagnostic test
Public and sustainable funding scheme
a sensitive and reproducible HPV test should detect the virus in all
women with disease or destined to develop it in the few years following a positive test. However, HPV is very common, particularly
among younger women, and more than 90% of infections regress
within two years regardless of the HPV type [20]. The real precursor
of cervical cancer is persistent HPV infection, which can be detected
with one of the following methods alone or in combination: (1)
testing women repeatedly for HPV; (2) restricting screening to
age groups where infections are more likely to represent persistent infections; or (3) detecting cytologic or visual abnormalities
associated with persistent infections. A series of potentially useful biomarkers including expression of E6/E7 transcripts, p16 and
others are under investigation and are discussed elsewhere in this
Monograph [21]. We discuss below some of the current screening
strategies that are currently considered to have potential to improve
the current programs.
3.1. Cytology as primary screening
Cytology has low and variable sensitivity, requires multiple visits and has proven extremely difcult to implement successfully in
LAC. Countries initiating programs need to consider new alternatives. However, screening with cytology is in use in many countries
in LAC, and transition to any different technique would take years.
In the meantime, where cytology is being used, quality assurance
must be emphasized. Quality assurance is more feasible when specialized staff are concentrated in as few laboratories as possible,
to assure uniformity of training, procedures, recommendations
to clinicians etc. In Costa Rica, for example, as part of the reorganization of the screening program, cytology laboratories were
centralized in 1998 into one large National Cytology Laboratory
that currently receives close to 400,000 smears a year. Since then,
cervical cancer incidence and mortality have decline signicantly,
probably as a consequence of this and other improvements of the
screening program (Fig. 2). In countries where centralized laboratories are not possible, cervical cancer screening guidelines should
include regulations for external and internal quality control, as well
as external regulatory supervision.
Another important aspect is the threshold for referral to colposcopy of lesions detected by cytology. LSIL is the cytological
manifestation of an acute HPV infection and not a true cancer precursor [22], and the vast majority of such lesions disappear in a
few months. When they are referred for colposcopy, they generate a large burden of referrals and treatment. When appropriate
follow-up can be assured, repeat cytology after six months should
be considered. Several organizations have modied their guidelines
in this regard, including the American Society for Colposcopy and
Cervical Pathology (ASCCP), which now recommends repeat cytol-
L55
Fig. 2. Standardized mortality rates of cervical cancer in Costa Rica, 19802005. Instituto Nacional de Estadstica y Censo, Registro Nacional de Tumores.
(India, Brazil, and Zimbabwe) have shown lower sensitivity, pointing to technical difculties in those settings [28]. HPV testing has
been approved by the USA FDA as an adjunct to cytology among
women aged 30 and older, where specicity is highest, allowing
for an extension of the screening interval given the very high negative predictive value of a negative HPV combined with negative
cytology. In younger women infection is highly prevalent and normally clears within the rst few months [29]. However, the ideal
age needs to be adapted to the age of initiation of sexual activity and the epidemiology of cervical cancer precursors of different
regions.
Several studies have been conducted in LAC [7,10,30,31], and it
has been shown that the predictive value of a negative HPV test is
very high (9798%) [32]. In this context, screening intervals may
be increased for HPV negative women, because their risk of developing cervical cancer over the following 510 years is very low
[33]. Also screening could be stopped or intervals increased among
repeatedly HPV negative women over 50.
In two recent large randomized trials comparing cytology alone
with cytology plus HPV testing conducted in The Netherlands [34]
and Sweden [35], a signicant reduction in the number of CIN3+
lesions after 46 years of follow-up in the groups receiving both
tests compared to the group receiving only cytology was observed,
further indicating that screening intervals could be extended.
It is clear that combining HPV and cytology represents an
improvement that leads to earlier detection of precursor lesions
and allows extension of the screening interval, but an approach
combining HPV and cytology would be costly and appears unrealistic for LAC. HPV testing alone followed by colposcopic referral
would produce a large number of referrals, given that it has limited specicity, and therefore HPV testing followed by triage with
a more specic test has been proposed (see below).
A note of caution is necessary when recommending HPV testing
for use in screening programs. At this time, the only fully validated
and FDA approved HPV testing method, which has been used in
most of the studies is HC2. It is highly desirable to have additional
comparable tests, but they need to be properly validated and certied to assure the anticipated benets of relying on a new technique.
The Pan American Health Organization (PAHO) and other international organizations would be expected to play an important role
in dening guidelines, negotiations for purchase of reagents and
certication of laboratories.
The high cost and relative technical complexity of HC2 make
it currently unrealistic for low-resources settings. A new simpler,
faster HPV test is being developed by PATH (Seattle, USA) in collaboration with Qiagen Gaithersburg, Inc., MD, USA (previously Digene
L56
ate results), but also of its limitations such as low sensitivity, poor
specicity and the need of frequent screenings (13 years intervals). VIA requires signicant training and supervision. Despite its
limitations, VIA can be a good alternative in areas where other techniques are not available or have not been successful (poor coverage,
decient quality, etc.), and it could serve as an initial platform to
develop screening activities that can later incorporate more effective techniques.
3.4. HPV testing followed by Pap smear
Approximately 5 to 20% of women are HPV positive [48]. Therefore, more than 80% of all women screened are HPV negative and
have very low-risk of cervical neoplasia in the following 510 years
[33]. A screening algorithm with HPV testing as the initial screening test, followed by cytology of HPV positives, which is a more
specic test, has been proposed [27,37]. Since well-trained cytologists and cytopathologists are scarce, those resources could be
employed for secondary evaluation of HPV positive women. The
main limitation of using Pap smear after HPV testing, in addition to
its limited sensitivity and dependence on human factors for quality,
is that unless the system is organized to collect both specimens at
the same time (reex testing), the results are not immediately available and women should have at least two visits before colposcopy
and treatment.
Women with negative cytology would need to be re-screened
with HPV testing at 612 months and if persistently positive
referred to colposcopy. Women with normal colposcopy would also
require close follow-up with repeat HPV testing. Where LBC is used,
reex testing is facilitated and cytology can be done on the same
specimen collected for HPV testing. This approach could also be
feasible where conventional cytology is used if both specimens are
collected at the same visit. In areas of LAC where cytology screening
has achieved demonstrated efcacy, this strategy could be implemented in demonstration projects.
3.5. HPV testing followed by VIA
Similar to the strategy described for HPV plus cytology, VIA could
be performed only in HPV positive patients, a strategy with the
advantage of saving time and one clinic visit. There are two possible
uses for VIA in this approach, triage and diagnosis.
The rationale for using VIA for triage of HPV infected women is
that visual evaluation of the cervix is poorly sensitive for detecting
CIN2+, especially if the lesions are small, as has been shown for colposcopy, which has an accuracy that seems to be much lower than
assumed before [4953]. An interesting study from South Africa
[54] provides an example of the use of VIA as a triage tool. Using
a very simple approach, women were randomized to one of three
study arms: (1) HPV testing: women with a positive test had triage
with VIA followed by cryotherapy unless this method revealed contraindications for cryotherapy such as suspicion of cancer, large
intraepithelial lesions, etc. that prompted to referal for specialized
evaluation; (2) conventional VIA followed by cryotherapy unless a
contraindication existed; and (3) control group followed with Pap
smear. After 12 months of follow-up, they found that the prevalence of CIN2+ lesions in the HPV testing plus cryotherapy group
was lower than in the other groups.
Using VIA as a diagnostic test for HPV infected women is more
complex than the previous approach. There would not be doubts
about the need of treating HPV positive women if VIA is positive,
but the decision becomes more complicated if VIA does not nd
abnormal changes in the cervical epithelium because, as previously
described, it could be missing early CIN2+ lesions. One option could
be to repeat the HPV test in one year and treat all women with
4. Conclusions
Immediate action needs to be taken in LAC to reduce the enormous burden of cervical cancer. We strongly recommend that each
country establishes a properly staffed and funded group dedicated
to cervical cancer control, responsible for developing and monitoring all activities of the program, including strict evaluation of the
compliance of all health providers. Screening and treatment should
be provided free of charge to all women. The different areas in the
country should be categorized according to their level of development and infrastructure to dene specic interventions to be
implemented in each area.
In places where no other methods are available or the existing
options have poor quality and limited coverage, we recommend
the implementation of visual inspection by primary care nurses
or physicians, with cryotherapy of positives after proper referral of
possible invasive cancers. The emphasis should be on complete coverage of women older than 2530 years, and implementation could
start with smaller demonstration projects. A VIA-based screening program still requires most of the programmatic components
described above and the use of VIA should be considered as an
interim approach while more sophisticated techniques such as HPV
testing can be introduced.
In areas where cytology is already established and has been
improved to the point of showing an impact on the incidence and
mortality, proper organization of the laboratories and, where feasible, centralization of the laboratories with the provision of adequate
equipment and quality assurance are paramount. Where followup can be assured, women with LSIL should be managed with
repeat cytology to prevent excessive burden to colposcopy services.
HSIL should be declared a public health priority with assurance of
follow-up and treatment for all women. Colposcopy services should
have the necessary staff, training, equipment and resources to evaluate and, if needed, treat in a timely fashion all women with HSIL.
Centralization of colposcopy services in high quality units should be
considered and such services should be restricted to women with
abnormalities and not used for primary screening.
In the near future, primary screening with HPV testing, with
its high sensitivity and negative predictive value should become
the standard of care, including algorithms using cytology or VIA
as secondary evaluations according to the local infrastructure and
resources. The new HPV test under development is expected to
be more affordable and to provide same-day results. All countries
should be aware of new developments in this eld, to incorporate
this promising technology when it becomes available. Demonstration projects and cost-effectiveness analysis are required, giving
serious consideration to self-collection of HPV specimens as an
alternative for women who live in isolated areas or refuse the
pelvic exam, and making sure only tests that have been properly validated are utilized. HPV testing will also be the method
of choice after mass vaccination is introduced. The collaboration
of governments, womens groups, academia, industry, donors and
international organizations could facilitate renewed efforts to control cervical cancer in LAC.
L57
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